CHARACTERIZATION ON THE BENCH OF AN AMIKACIN AEROSOL BEFORE CLINICAL-STUDIES

It has been suggested that nebulized antipseudomonas therapy may be of benefit in cystic fibrosis (CF) patients, Amikacin is effective again st Pseudomonas aeruginosa and does not contain sulfites, As a prelude to clinical studies that will use gamma camera techniques to quantify amikacin aerosol deposition, we present the characteristics of the ami kacin aerosol and demonstrate that labeling it does not change its dyn amics, Human serum albumin (HSA) was labeled with Tc-99m and was added to an amikacin solution (1 g per 8 mL and 1.5 g per 12 mL). Amikacin mixed with this tracer was charged in an ultrasonic nebulizer (Syst'Am LS; Villeneuve sur Lot, France), Low-resistance filters were connecte d between the nebulizer mouthpiece and a piston pump, The filters were changed after each 3-minute period during the 18-minute nebulization process, The mass of radiolabeled amikacin collected from each filter was measured by fluorescence polarization immunoassay (FPIA) and estim ated from Tc-99m countings, Particle size distribution, mass median ae rodynamic diameter (MMAD), and geometric standard deviation (sigma g) of the unlabeled and radiolabeled aerosols were measured by inserting a 10-stage cascade impactor between the nebulizer and the piston pump, The mass of amikacin that impacted on each stage was measured by FPIA for both unlabeled and radiolabeled aerosols, There was a close corre lation between FPIA and Tc-99m countings to measure the mass of radiol abeled amikacin deposited on filters (y = 1.32 x -1.91, r = 0.97, P < 0.0001), Maximum inhaled mass reached 30% of the nebulizer charge with the 1 g per 8 mL solution and 55% with the 1.5 g per 12 mL solution. There was also a close correlation between distribution of the unlabel ed and radiolabeled aerosols (y = 0.92 x + 0.74, r = 0.95, P < 0.0001) . MMAD (sigma g) was 3.0 (1.7) mu m. We conclude that it is possible t o produce an aerosol of amikacin that may deposit peripherally in the lungs, Labeling the drug does not alter the dynamic characteristics of the aerosol.